Lung cancer etiology is multifactorial, and growing evidence has indicated that long non-coding RNAs (lncRNAs) are important players in lung carcinogenesis. Duke University School of Medicine researchers performed a large-scale meta-analysis of 690,564 SNPs in 15,531 autosomal lncRNAs by using datasets from six previously published genome-wide association studies (GWASs) from the Transdisciplinary Research in Cancer of the Lung (TRICL) consortium in populations of European ancestry. Previously unreported significant SNPs (P value < 1 × 10-7) were further validated in two additional independent lung cancer GWAS datasets from Harvard University and deCODE. In the final meta-analysis of all eight GWAS datasets with 17,153 cases and 239,337 controls, a novel risk SNP rs114020893 in the lncRNA NEXN-AS1 region at 1p31.1 remained statistically significant (odds ratio = 1.17; 95% confidence interval = 1.11-1.24; P = 8.31 × 10-9). In further in silico analysis, rs114020893 was predicted to change the secondary structure of the lncRNA. This finding indicates that SNP rs114020893 of NEXN-AS1 at 1p31.1 may contribute to lung cancer susceptibility.

Manhattan plot of associations between
SNPs of the lncRNA genes and risk of lung cancer